International Conference on Harmonisation; Draft Document on Essential Documents for the Conduct of a Clinical Study; Availability

[Docket No. 94N-0197]

International Conference on Harmonisation; Draft Document on

Essential Documents for the Conduct of a Clinical Study; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is publishing a draft

document entitled ``Guideline for Essential Documents for the Conduct

of a Clinical Study.'' The draft document describes documents that

individually and collectively permit evaluation of the conduct of a

clinical study and the quality of the data produced. This document was

prepared by the Efficacy Expert Working Group of the International

Conference on Harmonisation of Technical Requirements for Registration

of Pharmaceuticals for Human Use (ICH). The draft document is intended

to help ensure that essential documents meet good clinical practice

standards and all applicable regulatory requirements. The concepts in

this draft document will later be incorporated into a larger document

on good clinical practices.

DATES: Written comments by October 11, 1994.

ADDRESSES: Submit written comments on the draft document to the Dockets

Management Branch (HFA-305), Food and Drug Administration, rm. 1-23,

12420 Parklawn Dr., Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT:

Regarding the draft document: Bette L. Barton, Center for Drug

Evaluation and Research (HFD-344), Food and Drug Administration, 7500

Standish Pl., Rockville, MD 20855, 301-594-1032.

Regarding the ICH: Janet Showalter, Office of Health Affairs (HFY-

20), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD

20857, 301-443-1382.

SUPPLEMENTARY INFORMATION: In recent years, many important initiatives

have been undertaken by regulatory authorities and industry

associations to promote international harmonization of regulatory

requirements. FDA has participated in many meetings designed to enhance

harmonization and is committed to seeking scientifically based

harmonized technical procedures for pharmaceutical development. One of

the goals of harmonization is to identify and then reduce differences

in technical requirements for drug development.

ICH was organized to provide an opportunity for tripartite

harmonization initiatives to be developed with input from both

regulatory and industry representatives. FDA also seeks input from

consumer representatives and others. ICH is concerned with

harmonization of technical requirements for the registration of

pharmaceutical products among three regions: The European Union, Japan,

and the United States. The six ICH sponsors are: The European

Commission, the European Federation of Pharmaceutical Industry

Associations, the Japanese Ministry of Health and Welfare, the Japanese

Pharmaceutical Manufacturers Association, FDA, and the U.S.

Pharmaceutical Research Manufacturers of America. The ICH Secretariat,

which coordinates the preparation of documentation, is provided by the

International Federation of Pharmaceutical Manufacturers Associations

(IFPMA).

The ICH Steering Committee includes representatives from each of

the ICH sponsors and the IFPMA, as well as observers from the World

Health Organization, the Canadian Health Protection Branch, and the

European Free Trade Area.

At a meeting held on October 27, 1993, the ICH Steering Committee

agreed that the following draft document entitled ``Guideline for

Essential Documents for the Conduct of a Clinical Study'' should be

made available for public comment. This draft document is the product

of the Efficacy Expert Working Group of the ICH. ``Essential

documents'' individually and collectively permit evaluation of the

conduct of a study and the quality of the data produced. The draft

document describes the purpose of each document and states whether the

document should be filed in the investigator's files or the sponsor's

files. Comments about this draft will be considered by FDA and the

Efficacy Expert Working Group of the ICH. Modifications will appear in

a larger draft document on good clinical practices. Ultimately, FDA

intends to adopt the ICH Steering Committee's final guidelines and

recommendations.

Although not required, FDA would normally provide at least a 75-day

comment period and preferably a 90-day comment period to provide

interested persons with ample time to review and comment upon this type

of an action. However, the comment period for this guideline has been

shortened to 60 days so that comments may be received by FDA in time to

be discussed at an October 1994 meeting involving this guideline.

Guidelines are generally issued under Sec. 10.90(b) (21 CFR

10.90(b)), which provides for the use of guidelines to state procedures

or standards of general applicability that are not legal requirements

but that are acceptable to FDA. The agency is now in the process of

revising Sec. 10.90(b). Therefore, this guideline if made final would

not be issued under current Sec. 10.90(b), and it would not create or

confer any rights, privileges, or benefits for or on any person, nor

would it operate to bind FDA in any way.

Interested persons may, on or before October 11, 1994, submit to

the Dockets Management Branch (address above) written comments on the

draft document. Two copies of any comments are to be submitted, except

that individuals may submit one copy. Comments are to be identified

with the docket number found in brackets in the heading of this

document. The draft document and received comments may be seen in the

office above between 9 a.m. and 4 p.m., Monday through Friday.

The text of the draft document follows:

Guideline for Essential Documents for the Conduct of a Clinical Study

Essential Documents are those documents which individually and

collectively permit evaluation of the conduct of a study and the

quality of the data produced. These documents serve to demonstrate

the compliance of the investigator, sponsor, and monitor with the

standards of Good Clinical Practice and with all applicable

regulatory requirements.

Essential Documents also serve a number of other important

purposes. Filing essential documents at the investigator and sponsor

sites in a timely manner can greatly assist in the successful

management and quality control of a study by the investigator,

sponsor, and monitor. These documents are also the ones which are

usually audited by the sponsor's quality assurance function or

inspected by a regulatory agency as part of the process to confirm

the validity of the study conduct and the integrity of the data

collected.

The minimum list of essential documents which has been developed

follows. The various documents are grouped in three sections

according to the stage of the study during which they will normally

be generated: (1) Before the clinical phase of the study commences,

(2) during the clinical conduct of the study, and (3) after the

completion or termination of the study. A description is given of

the purpose of each document, and whether it should be filed in

either the investigator or sponsor files or both. It is acceptable

to combine some of the documents, provided the individual elements

are readily identifiable.

Good Clinical Practice provides that trial master files be

established at the beginning of the study, both at the investigator

site and at the sponsor's office. The final close out visit of a

study can only be done when the monitor has reviewed both

investigator and sponsor files and confirms that all necessary

essential documents are in the appropriate files.

Any or all of the documents addressed in this guideline may be

subject to, and should be available for, audit by the sponsor or a

nominated independent organization and/or inspection by competent

authorities.

BILLING CODE 4160-01-F

E:\GRAPHICS\EN09AU94.007

E:\GRAPHICS\EN09AU94.008

E:\GRAPHICS\EN09AU94.009

E:\GRAPHICS\EN09AU94.010

E:\GRAPHICS\EN09AU94.011

E:\GRAPHICS\EN09AU94.012

E:\GRAPHICS\EN09AU94.013

E:\GRAPHICS\EN09AU94.014

E:\GRAPHICS\EN09AU94.015

E:\GRAPHICS\EN09AU94.016

E:\GRAPHICS\EN09AU94.017

E:\GRAPHICS\EN09AU94.018

Dated: August 3, 1994.

William K. Hubbard,

Acting Deputy Commissioner for Policy.

[FR Doc. 94-19360 Filed 8-8-94; 8:45 am]

BILLING CODE 4160-01-C